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Theoretical calculations were performed to investigate the mechanism and enantioselectivity of cinchonine–thiourea‐catalyzed intramolecular hetero‐Diels–Alder cycloaddition of ethynylphenol derivatives to afford axial chirality naphthalenylpyran products via a vinylidene ortho‐quinone methide (VQM) intermediate. The results show that this transformation occurs through a reaction pathway involving the deprotonation of the naphthol moiety by the quinuclidine base, intramolecular proton transfer in ammonium naphthalenolate, and [4+2] cycloaddition. It is found that the axial chirality of the VQM intermediate is generated by the protonation step, which affects the enantioselectivity of the reaction. The enantioselectivity for the generation of the VQM intermediate is controlled by steric repulsion with the cinchonine framework, which provides an R‐axial chirality VQM as the major intermediate. Moreover, the enantioselectivity for the axial chirality of the naphthopyran product is controlled by the cycloaddition step, in which an extra hydrogen bond between the naphthalenol and cinchonine moieties leads to a favorable configuration for the generation of the S‐axial chirality naphthopyran product. The calculated enantioselectivity and enantiomeric excesses coincide with experimental observations. [ABSTRACT FROM AUTHOR]

The possible mechanisms and origin of the enantioselectivity of the reaction between 2H‐azirine and an aldehyde catalyzed by an N‐heterocyclic carbene (NHC) were theoretically studied and predicted at the M06‐2X/6‐31G(d,p)/IEF‐PCMMTBE//M06‐2X‐GD3/6‐311++G(2df, 2pd)/IEF‐PCMMTBE level. The most favorable reaction pathway consists of four steps, i.e. complexation of the NHC and the aldehyde, stepwise [1,2]‐proton transfer, C−C bond formation coupled with another proton transfer, and recycling of the NHC. The computational results indicate that the stereoselectivity‐determining step is also the rate‐determining step, which is the third step (i.e. intermolecular addition). The calculated 99 % ee is very close to the experimentally observed value of 96 % ee, demonstrating that the calculations are reliable. Two important roles of the NHC were identified by global reaction index (GRI) analysis and natural population analysis (NPA), that is, realizing the umpolung reactivity of the aldehyde and facilitating the deprotonation of aldehyde. Moreover, the efficiency of different NHC catalysts can be mainly predicted by computing the nucleophilic index of the corresponding Breslow intermediates. Furthermore, distortion/interaction and noncovalent interaction (NCI) analyses revealed that the π⋅⋅⋅π interactions between the NHC and substrates were the key factor in the reaction enantioselectivity. [ABSTRACT FROM AUTHOR]

Palladium (Pd)‐catalyzed radical oxidative C−H carbonylation of alkanes is a useful method for functionalizing hydrocarbons, but there is still a lack of understanding of the mechanism, which restricts the application of this reaction. In this work, density functional theory (DFT) calculations were carried out to study the mechanism for a Pd‐catalyzed radical esterification reaction. Two plausible reaction pathways have been proposed and validated by DFT calculations. The computational results reveal that the generated alkyl radical prefers to add to the carbon monoxide (CO) molecule to form a carbonyl radical before bonding with the Pd species. Radical addition onto Pd followed by CO migratory insertion was unfavorable owing to the high energy barrier of the migratory insertion step. The regioselectivity of the C(sp3)−H carbonylation was also investigated by DFT. The results show that the regioselectivity is controlled by both the bond dissociation energy of the reacting C−H bond and the stability of the corresponding generated carbon radical. Competitive side reactions also affected the yield and regioselectivity owing to the rapid consumption of the stable radical intermediate. Carbonylation mechanism: DFT method M06‐L was used to investigate the mechanism of Pd‐catalyzed radical oxidative carbonylation of alkanes with alcohols to afford alkyl acid esters. The results show alkyl radicals prefer to add to the CO molecule to form a carbonyl radical before bonding with the Pd species. Regioselectivity is controlled by both the bond dissociation energy of reacting the C−H bond and the stability of the corresponding generated carbon radical. [ABSTRACT FROM AUTHOR]

Abstract: Organocatalysis has emerged as an effective strategy for chemical synthesis. Within this area, phosphine‐catalyzed coupling reactions have attracted considerable attention because of their versatility and wide range of applications in the construction of new C−C bonds. Recently, various experimental studies on the phosphine‐catalyzed coupling reaction of allenes have been reported, and mechanistic and computational studies have also progressed considerably. As a nucleophile, phosphine can react with an allene to form a zwitterionic phosphoniopropenide intermediate. After stepwise cycloaddition and proton transfer, the phosphine catalyst can be regenerated by C−P bond cleavage. Alternatively, the zwitterionic phosphoniopropenide intermediate could also be protonated by a Brønsted acid to generate a phosphonium intermediate, which can be used to construct new C−C bonds by electrophilic addition. In this review, we have summarized details of mechanistic studies of phosphine‐catalyzed allene coupling reactions that follow these two reaction modes. In addition to detailing the reaction pathway, the regioselectivity and diastereoselectivity of the phosphine‐catalyzed allene coupling reaction are also discussed in this review. [ABSTRACT FROM AUTHOR]